Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

Traction force against the substrate is required for neuronal migration, but how it is generated and regulated remains controversial. Using traction force microscopy, we showed in cultured granule cells the coexistence of three distinct contraction centers (CCs) that are located at the distal and proximal regions of the leading process as well as at the trailing process, regions exhibiting high-level myosin-II activities. The CC activities depended on myosin-II, actin filaments, and microtubules, as well as substrate adhesion, and exhibited apparently independent fluctuation. The difference of strain energies associated with CC activities between leading versus trailing processes tightly correlated with the displacement of the soma at any given time. Application of brain-derived neurotrophic factor (BDNF) and Slit2, factors known to guide neuronal migration, at the leading process altered CC activities by regulating the small GTPases Cdc42 and RhoA, respectively, leading to forward and rearward soma translocation. These results delineate the multiple origins and spatiotemporal dynamics of the traction force underlying neuronal migration.